PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genes, MHC Class II”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1995

Isotype-specific regulation of MHC class II gene expression in human monocytes by exogenous and endogenous tumor necrosis factor.

The control of expression of MHC class II molecules on antigen-presenting cells is important for the induction of immunity, while aberrant expression of these molecules plays a role in the immunopathology of autoimmune diseases. This study explored the role of tumor necrosis factor alpha (TNF) in controlling the level of HLA class II mRNA in human monocytes. Exposure of monocytes to exogenous recombinant TNF (rTNF) selectively up-regulated DR alpha-mRNA but not DP or DQ alpha-mRNA. Inhibitors of TNF synthesis, pentoxifylline (PTX) and thalidomide, inhibited TNF mRNA accumulation in LPS-activated monocytes and down-regulated DR mRNA but not DP or DQ mRNA. The inhibitory effect of anti-TNF monoclonal antibody (MAb) indicated that endogenously generated TNF acted extracellularly. Anti-p75 TNF-R2 receptor and to a lesser extent anti-p55 TNF-R1 MAbs inhibited TNF-mediated up-regulation of DR mRNA and TNF mRNA. Taken together, this implies that endogenously generated TNF plays a role in controlling isotype-specific MHC class II gene expression in human monocytes/macrophages. These results may have some implications for anti-tumor response and autoimmunity.

Antibodies, Monoclonal↗
PubMed1997

Regulation of transcription of MHC class II genes.

Genetic and biochemical analyses have identified multiple DNA-binding and non-DNA-binding proteins that functionally regulate MHC class II genes. These include RFX, X2BP, NF-Y, CIITA, OCT-2 and Bob1. One of the essential non-DNA-binding proteins, CIITA, appears to function as a limiting molecular switch that is responsible for the control of class II expression and the regulation of expression by interferon-gamma.

Gene Expression Regulation↗
PubMed2002

Increase of the stimulatory effect of dendritic cells by pulsing with apoptotic bodies transfected with the MHC class II gene.

Dendritic cells (DC) are capable of capturing and processing antigens and can stimulate co-cultured effector cells in a specific manner. Here, we pulsed DC with apoptotic bodies (apb) from colorectal carcinoma. For enhancement of the immunogenic potential of apb, we transduced the tumor cells with the MHC class II gene before irradiation. After transfection, tumor cells, which are normally MHC class II negative, expressed MHC class II in 26.3%. Staining apb with PKH-2 and DC with PKH-26, we determined an apb-uptake of 27.6% by DC. Lytic activity of effector cells cocultured with DC pulsed with MHC class II transduced apb against the donor cell line at an effector to target ratio of 40:1 was 43.8% compared to 35.3% for pulsing with mock transduced cells. Secretion of interleukin-12 (IL-12) by DC was significantly enhanced after pulsing with MHC class II transduced apb compared to DC pulsed with mock transduced apb. Coculture with apb-pulsed DC led to an increase of proliferation rate and can stimulate effector cells in a specific manner. The immunogenic potential could be enhanced by transducing tumor cells with the MHC class II gene.

Apoptosis↗
PubMed1998

Differential expression of MHC class II genes in lung tumour cell lines.

Molecular characterization of HLA class II expression was investigated in five lung tumour cell lines at the protein and mRNA levels. The cell lines exhibited a differential expression of HLA-DR, HLA-DP and HLA-DQ products and also showed differences in the inducibility of HLA class II genes by gamma-IFN. Gamma-IFN stimulation induced only HLA-DR expression to varying degrees in three cell lines, while only one cell line showed stimulation for HLA-DP and none for HLA-DQ antigens. These results suggest locus-specific regulation for the three loci. The presence of DR protein on the cell-surface membrane was always positively correlated with the presence of HLA-DR mRNA in the cells. After treatment with 5-azacytidine in the A549 cell line, which expressed the lowest values, there was no effect on HLA class II levels. This suggested that methylation does not play an important role in the lack of MHC class II antigen expression. In addition to studying mRNA levels of HLA class II antigens, we analysed mRNA of the proto-oncogene c-myc and observed a positive correlation of two mRNA: the increments in HLA-DR expression were associated with increments in c-myc expression. This suggests a relationship between the regulatory and HLA-DR antigens control the expression of c-myc and HLA-DR antigens in lung tumour cell lines.

Actins↗
PubMed1994

Molecular analysis of G1B and G3A IFN gamma mutants reveals that defects in CIITA or RFX result in defective class II MHC and Ii gene induction.

Class II major histocompatibility complex (MHC) genes and the invariant (Ii) gene are inducible by interferon-gamma (IFN gamma) but not by interferon-alpha and interferon-beta. The promoter regions of these genes contain three regulatory elements that mediate constitutive and IFN gamma-induced expressions; however, none of the DNA-binding proteins that interact with these elements are regulated by IFN gamma. Recently, a gene coding for a transactivator (CIITA) of class II MHC genes that complements a HLA-DR-negative immunodeficiency has been isolated. Using one IFN gamma mutant cell line (G3A) that is selectively defective in HLA-DR and Ii induction, four lines of evidence are presented to show that CIITA mediates the IFN gamma induction of HLA-DR and Ii genes. Analysis of another mutant line, G1B, indicates that the lack of DRA and Ii gene induction by IFN gamma is correlated with the lack of RFX DNA binding activity, thus providing the link between RFX and an IFN gamma response.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1995

How are class II MHC genes turned on and off?

Fragments of foreign antigen are detected by CD4+ helper T cells via the T cell receptor for antigen in the context of major histocompatibility complex (MHC) class II molecules. Very few cells normally express class II MHC molecules, and these cells play critical roles in antigen presentation and in the thymic selection of T lymphocytes before their exit into the periphery. Because of the central role the class II MHC molecules play in immune system function, it is not surprising that the lack of expression of these molecules results in a severe combined immunodeficiency disorder (called bare lymphocyte syndrome) and that the aberrant expression of the molecules is frequently observed in the target organs of various autoimmune disorders (e.g., multiple sclerosis and rheumatoid arthritis). Because both classes of disease could conceivably be treated by molecular approaches targeted at either restoring or inhibiting expression of class II MHC genes, there has been an intense effort during the past decade to elucidate the regulatory mechanisms of class II MHC genes. An analysis of recent advances in this effort is provided in this review article.

Animals↗
PubMed2000

Methylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control.

Inhibition of class II trans-activator (CIITA) expression prevents embryonic trophoblast cells from up-regulating MHC class II genes in response to IFN-gamma. This is thought to be one mechanism of maternal tolerance to the fetal allograft. The CIITA gene is regulated by four distinct promoters; promoter III directs constitutive (B cell) expression, and promoter IV regulates IFN-gamma-inducible expression. Using in vivo genomic footprinting, promoter-reporter analysis, Southern blot analysis, and RT-PCR, we have examined the cause of CIITA silencing in a trophoblast-derived cell line. We report here that methylation of promoter IV DNA at CpG sites in Jar cells prevents promoter occupancy and IFN-gamma-inducible transcription. The inhibition of CpG methylation in Jar cells by treatment with 5-aza-2'-deoxycytidine restores IFN-gamma inducibility to CIITA. This is the first description of an epigenetic mechanism involved in regulation of CIITA and MHC class II gene expression.

Antimetabolites, Antineoplastic↗
PubMed2005

Characterization of MHC class II genes from an ancient reptile lineage, Sphenodon (tuatara).

The organization and evolution of major histocompatibility complex (MHC) genes vary considerably among vertebrate lineages. MHC genes have been well characterized in mammals, birds, amphibians and fish, but little is known about their organization in reptiles, despite the fact that reptiles occupy an important phylogenetic position for understanding the evolutionary history of both mammalian and avian MHC genes. Here we describe the characterization of the first MHC class II B cDNA sequences from a non-avian reptile, the tuatara (Sphenodon spp.). Three class II B sequences were isolated from a tuatara cDNA library, and four additional partial sequences were isolated by reverse transcriptase-polymerase chain reaction. Six of these sequences appear to belong to the same gene family, which we have named SppuDAB. The remaining sequence (named SppuDBB) shares only 43.9% amino acid similarity with SppuDAB and thus appears to represent a separate gene family. SppuDBB may be a non-classical locus as it does not contain all the conserved residues expected of a classical MHC class II gene. Southern blot analysis indicates that only a single copy of SppuDBB exists in tuatara, but that multiple loci related to SppuDAB are present. The SppuDAB sequences have the highest amino acid similarity (57.2-62.4%) with class II B sequences from the spectacled caiman, but only 26.4-48.7% similarity with sequences from other vertebrates. The tuatara sequences do not strongly group with other reptile sequences on a phylogenetic tree, reflecting the antiquity of the Sphenodon lineage and the lack of closely related sequences for comparison.

Amino Acid Sequence↗
PubMed1992

Inhibition of class II MHC gene expression by anti-sense RNA in transgenic mice.

We have established transgenic mice carrying the anti-sense DNA to the gene encoding beta chain of the class II major histocompatibility complex (I-A) molecule. The amount of I-A molecule on splenic B lymphocytes from the mice was reduced in the presence of a large amount of the exogenous anti-sense RNA. The amount of I-A beta chain RNA was selectively reduced and inversely correlated with the amount of anti-sense RNA in the spleens. These results suggest that the I-A beta chain RNA is rapidly degraded by duplex formation with the anti-sense RNA in splenic B cells from the transgenic mice.

Animals↗
PubMed2001

Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter.

In melanoma cell lines, two different patterns of MHC class II expression have been described, either an IFN gamma-inducible expression of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ, resembling that described for melanocytes, or a constitutive expression, i.e., IFN-gamma independent, of all three HLA-D isotypes. As this latter phenotype has been associated with a more rapid progression of melanoma tumors, we have analyzed in different melanoma cell lines the molecular mechanisms leading to this abnormal pattern of MHC class II expression. In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines, we have shown the constitutive expression of CIITA (class II transactivator) transcripts, CIITA being known as the master switch of MHC class II expression. Unexpectedly, these transcripts initiate from promoter III of the CIITA gene, a promoter that is mainly used constitutively in B lymphocytes. This expression was further shown to occur through factor(s) acting on the enhancer located upstream of CIITA promoter III, which was previously described in epithelioid cells as an IFN-gamma-response sequence. The hypothesis of a general abnormality of the IFN-gamma transduction pathway was dismissed. Constitutive transcription of CIITA from promoter III having been observed in unrelated melanoma cell lines, we propose the hypothesis that this phenomenon might not be a random event, but could be linked to the neoplasic state of the melanoma cells.

5' Untranslated Regions↗
PubMed1989

Specific inhibition of class II MHC gene expression by anti-sense RNA.

We have established an anti-sense RNA system which is capable of regulating expression of the class II (Ia) molecule coded for by the major histocompatibility complex in cultured mouse cells. Various areas of the I-A beta chain gene were subcloned in an anti-sense orientation to the 3' of the dihydrofolate reductase (DHFR) cDNA under the control of the human metallothionein IIa gene promoter. These anti-sense DNA constructs were transfected into M12.4 cells, a BALB/c B lymphoma cell line which expresses both I-A and I-E molecules on the cell surface. I-A expression of selected clones transfected with anti-sense DNA encompassing the 5' untranslated region (UT) (100 or 310 bp) including the translation start site or the poly(A) addition signalling sequence in the 3' UT (250 bp) of the I-A beta chain gene were specifically reduced to less than 5% of the control M12.4 cell surface I-A expression. These clones had normal levels of I-E expression. However, transfection of the anti-sense DNA to the beta 1 domain (510 bp) including the splicing donor and acceptor sequences did not affect the expression of I-A molecules. The same antisense DNA constructs (100 bp of the 5' UT or 250 bp of the 3' UT) without the DHFR cDNA (710 bp) did not down-regulate the expression of I-A molecules, indicating that either the physical length of the anti-sense RNA or specific DHFR cDNA sequences are also important.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Protective modulation of class II MHC gene expression in tubular epithelium by target antigen-specific antibodies. Cell-surface directed down-regulation of transcription can influence susceptibility to murine tubulointerstitial nephritis.

We have been studying the factors which permit autoimmune injury to the kidney leading to interstitial nephritis. Nonsusceptible mice develop L3T4+ effector T cells which do not recognize their 3M-1 target Ag, nor produce interstitial lesions in the kidney unless proximal tubular class II MHC Ag expression is increased, for example, by rIFN-gamma. Anti-tubular basement membrane/alpha 3M-1-Ab, normally present in such mice after immunization with 3M-1, produce an opposite result by diminishing class II transcription and expression. This unique antibody-ligand interaction on the surface of proximal tubular epithelium secreting 3M-1 serves as a novel protective regulatory response in interstitial parenchyma. The in vitro studies conveyed in this current report suggest that alpha 3M-1-Ab mediate this protective effect by reducing the transcription of mRNA encoding class II gene products. These findings, within the overall complexity of a nephritogenic immune response, demonstrate the important role certain elements may play in maintaining functional nonsusceptibility to autoimmune injury.

Animals↗
PubMed2004

The DY genes of the cattle MHC: expression and comparative analysis of an unusual class II MHC gene pair.

The major histocompatibility complex of cattle (BoLA) contains the class II genes DYA and DIB which are transcribed with a dendritic cell restricted distribution. As part of the process to determine whether these genes have any functional significance, we demonstrate that they form a closely linked pair characteristic of other expressed class II MHC molecules. Accepted nomenclature convention suggests that BoLA-DIB should therefore be renamed BoLA-DYB. Analysis of the first full-length DYA and DYB transcripts revealed open reading frames with potential to translate 253 and 259 amino acid proteins, respectively. Comparative sequence analysis between the DY polypeptides and classical cattle, human and mouse class II MHC alpha and beta polypeptide chains revealed 16 unique amino acid residues at positions predicted to form and line the putative peptide-binding region. Expression of tagged constructs demonstrates for the first time that the DY genes of cattle are capable of translating distinctive class II MHC alpha and beta polypeptide chains.

Amino Acid Sequence↗
PubMed1994

Characterization of astrocyte nuclear proteins involved in IFN-gamma- and TNF-alpha-mediated class II MHC gene expression.

IFN-gamma is a potent inducer of class II MHC Ags on different cell types, including the astrocyte. TNF-alpha alone has no effect on class II MHC expression, but enhances IFN-gamma-induced class II expression. IFN-gamma acts by inducing transcription of the class II gene, and TNF-alpha enhances the rate of IFN-gamma-induced transcription. We have previously described two factors, IFN-gamma-enhanced factor X (IFNEX) and TNF-alpha induced complex X (TIC-X), whose expression is induced by IFN-gamma and IFN-gamma/TNF-alpha, respectively, which interacted with the X box of the DRA promoter. In this study, we show that IFNEX and TIC-X bind to the X2 core, with contacts extending into the 3' end of X1 and into the spacer region of the DRA promoter. We also show a functional correlation between binding activity and transcriptional activity of the DRA promoter. These results strongly suggest that both IFNEX and TIC-X play important roles in the regulation of class II MHC gene expression in the astrocyte.

Animals↗
PubMed2000

The expression of MHC class II genes in macrophages is cell cycle dependent.

Using different drugs, we stopped the cell cycle of bone marrow-derived macrophages at different points. After IFN-gamma stimulation, macrophages arrested at the G(1) phase of the cell cycle did not increase cell surface expression of the MHC class II IA. This inhibition is specific, because, under the same conditions, IFN-gamma induces the expression of Fcgamma receptors and the inducible NO synthase mRNA. Treatments that inhibit macrophage proliferation by blocking the cell cycle at the G(1) phase, such as adenosine, forskolin, or LPS, blocked the IFN-gamma induction of IA. Under IFN-gamma treatment, the steady-state levels of IAalpha and IAss mRNA did not increase in cells arrested at the G(1) phase and the half-life of the MHC mRNA was not modified. These data suggest that the cell cycle modulation of IFN-gamma-induced MHC II gene expression occurs at the transcriptional level. The expression of the class II transactivator mRNA induced by IFN-gamma was also blocked when macrophages were arrested at the G(1) phase of the cell cycle, suggesting that the lack of IFN-gamma response occurs at the early steps of MHC class II expression. Finally, macrophages arrested at the G(1) phase showed increased basal levels of cell surface IA due to an increase of the translational efficiency. These data show that the expression of MHC class II genes is regulated by the cell cycle.

Animals↗